Testa M, Yeh M, Lee P, Fanelli R, Loperfido F, Berman J W, LeJemtel T H
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Am Coll Cardiol. 1996 Oct;28(4):964-71. doi: 10.1016/s0735-1097(96)00268-9.
This study sought to determine the circulating levels of cytokines and their respective endogenous modulators in patients with congestive heart failure of variable severity.
Activation of immune elements localized in the heart or periphery, or both, may promote release of cytokines in patients with congestive heart failure. Although an increased circulating level of tumor necrosis factor-alpha (TNF-alpha) and its soluble receptor type II (sTNF-RII) is well documented, less is known about other cytokines (i.e., interleukin-1-beta [IL-1-beta], interleukin-6 [IL-6] and interleukin-2 [IL-2] and their soluble receptor/receptor antagonists).
Circulating levels of TNF-alpha and sTNF-RII, IL-1-beta, IL-1 receptor antagonist (IL-1-Ra), IL-6, IL-6 soluble receptor (IL-6-sR), IL-2 and IL-2 soluble receptor-alpha were measured using enzyme-linked immunosorbent assay kits (Quantikine, R&D Systems) in 80 patients with congestive heart failure due to coronary artery disease or hypertension. The severity of their symptoms, which ranged from New York Heart Association functional class I to IV, was confirmed by measurement of peak oxygen consumption.
The percentage of patients with elevated levels of cytokines and their corresponding soluble receptor/receptor antagonists significantly increased with functional class. For TNF-alpha and IL-1-beta, the percentage of patients with elevated levels of soluble receptor/receptor antagonists was higher than that of patients with elevated levels of the cytokine itself. For IL-6, the percentage of patients with elevated levels of IL-6-sR tended to be lower than that of patients with elevated levels of IL-6. All but two patients had undetectable levels of IL-2, and all but seven had levels of IL-2-sR within a normal range.
In patients with congestive heart failure, circulating levels of cytokines increased with the severity of symptoms. In these patients, circulating levels of sTNF-RII and IL-1-Ra are more sensitive markers of immune activation than are circulating levels of TNF-alpha and IL-1-beta, respectively. Levels of IL-2 and IL-2-sR are not elevated when congestive heart failure is due to coronary artery disease or hypertension.
本研究旨在测定不同严重程度的充血性心力衰竭患者体内细胞因子及其相应内源性调节剂的循环水平。
心脏或外周或两者中免疫成分的激活可能促使充血性心力衰竭患者释放细胞因子。虽然肿瘤坏死因子-α（TNF-α）及其可溶性II型受体（sTNF-RII）循环水平升高已有充分记录，但对于其他细胞因子（即白细胞介素-1-β [IL-1-β]、白细胞介素-6 [IL-6] 和白细胞介素-2 [IL-2]）及其可溶性受体/受体拮抗剂了解较少。
使用酶联免疫吸附测定试剂盒（Quantikine，R&D Systems）测定80例因冠状动脉疾病或高血压导致充血性心力衰竭患者的TNF-α、sTNF-RII、IL-1-β、IL-1受体拮抗剂（IL-1-Ra）、IL-6、IL-6可溶性受体（IL-6-sR）、IL-2和IL-2可溶性受体-α的循环水平。通过测量峰值耗氧量确认其症状严重程度，范围从纽约心脏协会心功能分级I级到IV级。
细胞因子及其相应可溶性受体/受体拮抗剂水平升高的患者百分比随功能分级显著增加。对于TNF-α和IL-1-β，可溶性受体/受体拮抗剂水平升高的患者百分比高于细胞因子本身水平升高的患者。对于IL-6，IL-6-sR水平升高的患者百分比往往低于IL-6水平升高的患者。除两名患者外，所有患者的IL-2水平均检测不到，除七名患者外，所有患者的IL-2-sR水平均在正常范围内。
在充血性心力衰竭患者中，细胞因子的循环水平随症状严重程度增加。在这些患者中，sTNF-RII和IL-1-Ra的循环水平分别比TNF-α和IL-1-β的循环水平更敏感地反映免疫激活。当充血性心力衰竭由冠状动脉疾病或高血压引起时，IL-2和IL-2-sR水平不会升高。
